The activation of the coagulation system, ultimately leading to the formation of a fibrin clot, is the primary pathogenetic event in all thrombotic diseases and is often associated with blood vessel diseases and inflammatory reactions. Recovery from these pathological events necessitates vessel diseases and inflammatory reactions. Recovery from these pathological events necessitates the effective dissolution of the fibrin deposit, fibrinolysis, and the restoration of vascular integrity. Clearly, the plasminogen system is a major pathway for the catabolism of fibrin, but other alternative fibrinolytic systems may play a significant role in the dissolution of intravascular and extravascular fibrin deposits. Such alternative pathways for fibrinolysis may play important roles in the control of coagulative processes, in the resolution of events associated with disease processes, and ultimately in the maintenance of normal health. The present proposal is intended to develop a clear understanding of the alternative fibrinolytic pathway present in leukocytes. These studies will establish the structural and immunochemical changes induced in the fibrinogen and fibrin substrates by the fibrinolytic leukocyte proteases. The number, identity, and characteristics of the fibrinolytic leukocyte proteases will be established and the effect of each upon the fibrin and fibrinogen substrates will be established. The biological activities of the fragments generated by these enzmes will be considered in terms of their effects on the coagulation system, the immune system, the platelet, and the inflammatory systems. With an understanding of the components of this system, it will be possible then to examine the role of this system in health and in disease. BIBLIOGRAPHIC REFERENCES: Plow, E.F. and Edgington, T.S.: An alternative pathway for fibrinolysis. I. The cleavage of fibrinogen by leukocyte proteases at physiological pH. J.Clin. Invest. 56: 30-38, 1975.